Amino acids are used in, inter alia, parenteral or animal nourishment, organic syntheses (e.g., in polymer chemistry), and as synthetic structural elements for the preparation of pharmaceutical products. Because of their importance in the area of polymer chemistry, O-amino acids have received a particularly large amount of attention and many methods for the synthesis of these compounds have appeared in the literature. For example, O-amino octanoic acid can be produced from cyclooctanone by Beckmann rearrangement with subsequent ring opening (WO 9850341; Synth. Commun. 31:2047-2050 (2001); Synth. Commun. 28:2275-2280 (1998); Synth. Commun. 16:2641-2649 (1996); J. Chem. Soc., Chem. Commun. 1101 (1995); Synthesis 537-538 (1979); Can. J. Chem. 70:86-196 (1992)). In addition, other Beckmann rearrangements can be performed starting from longer-chain, aliphatic oximes (Chem. Ber. 29:806-809 (1896); Chem. Ber. 27:3121-3129 (1894); J. Chem. Soc. 105:2809 (1914); J. Chem. Soc. 2207 (1926)). O-amino octanoic acid can also be synthesized by the unilateral Hoffmann degradation of azelaic acid (Chem. Ber. 89:177-120 (1956)) or by Curtis rearrangement of an azelaic acid monoalkylester (Chem. Pharm. Bull. 7:99-100 (1959)). Other methods described in the literature include: synthesis by hydrogenation of 7-cyanoheptanoic acid (Izv. Akad. Nauk. USSR, Ser. Khim. 224-229 (1955), Engl. edition 199-205); by hydrogenation of 7-cyano-2,5-heptadienic acid (DE 1081469; Agnew. Chem. 72:74-76 (1960)); by reacting 8,8-dichloro-7-octenyl amine with aqueous sulfuric acid (Zh. Obshch. Khim. 27:2418-2421 (1957), Engl. edition 2481-2484); and by reacting the corresponding O-chlorocarboxylic acid with liquid ammonia (FR 1346045). All of these methods either suffer from poor accessibility of reactants, have low reaction yields, or cannot practically be carried out on a large scale.
The reaction of a halogenated carboxylic acid ester with alkali metal cyanates in the presence of an alcohol and subsequent double saponification of the formed urethane carbonic acid ester to amino acid has been suggested in the literature (DE 2854627; Agnew. Chem. 91:504-505 (1979); Chem. Ber. 114:173-189 (1981)). In particular, authors report the synthesis of amino acids by the reaction of bromo- or chloro-substituted carbonic acid esters in polar aprotic solvents with alkali metal cyanate in the presence of an alcohol to form urethane. This then undergoes acidic hydrolysis. However, only the use of comparatively short-chain halogenated carboxylic acid esters, i.e., with a maximum chain length of six carbon atoms, is described. Nothing is reported concerning the synthesis of higher-chain derivatives. Moreover, the disclosed method will require substantially longer reaction times for the conversion of chlorocarboxylic acid esters to urethane than for the conversion of the corresponding bromocarboxylic acid esters. For example, 6-chlorohexanoic acid methylester requires 30 hours of reaction time for a complete conversion to 6-(methoxycarbonylamino)-hexanoic acid methylester, whereas 6-bromohexanoic acid methylester is completely converted after only 0.75 hours. Since chlorine compounds are generally preferred in large scale industrial syntheses, this is a serious drawback. In addition, the hydrolytic splitting of the urethane group using a mixture of formic acid and hydrochloric acid in water appears to require 24 hours of heating at reflux temperature. This would also make the procedure generally undesirable for large-scale use.